Research Interests

In our laboratory, we utilize computational methods and biophysical experiments to study the properties and behavior of biomacromolecules and biomolecular complexes. Techniques used range from interactive computer graphics model building to computer simulation of molecular motions. Computational methods complement experimental techniques and can enhance our understanding of biomacromolecular function.

Our current research interests are focused in several key areas. One area of research involves the use of interactive computer graphics and simulation methods to investigate protein-ligand complexes. The goal of these studies is to provide detailed molecular models for ligand-macromolecule recognition and binding processes. These studies can also suggest structural modifications for ligands (or biomacromolecules) that may enhance desired biological effects.

A second area of research employs computational techniques and biophysical experimental methods to aid in three-dimensional model construction and refinement of protein structures. The principal effort in this area focuses on integral membrane (i.e., membrane embedded) protein structure model building. Integral membrane proteins pose immense challenges for experimental structure determination, so computational approaches can make important contributions to a greater understanding of structure/function relationships in these proteins. One project involves study of G protein-coupled receptors, with special emphasis on adrenergic neurotransmitter receptors. In this study, we are especially interested in structural attributes that control receptor subtype ligand binding selectivity. Another project involves a detailed study of class II major histocompatibility complex (MHC) proteins. In this project, we are investigating correlations of MHC haplotypes with chemical property variations and autoimmune disease associations, such as insulin-dependent diabetes mellitus, rheumatoid arthritis, and myasthenia gravis. A final project involves an examination of structure-function relationships of bacterial chemotaxis receptors.

A final area of major research activity concerns the development of new mathematical models and computer software to aid in modeling studies such as those outlined above. Much effort at present involves the development of methods to calculate molecular properties, especially solvent effects and binding free energies for ligand-receptor complexes, more accurately in simulations. We also develop algorithms for analysis and graphical display of simulation results.